Optical system for measuring metabolism in a body and imaging method

ABSTRACT

In an optical measurement system and imaging method adapted to measure in vivo information in a living body without harming the living body, light rays of a plurality of wavelengths which are modulated in intensity with a plurality of different frequencies are irradiated on a plurality of irradiation positions on the surface of a living body, and time-variable changes in living body transmitting light intensity levels corresponding to the respective wavelengths and the respective irradiation positions are measured at different positions on the surface of the living body. Light is utilized to image the results of the measurements, in which the measuring time is shortened by estimating fluctuation attributable to the living body, and the presence or absence of a change in measured signal can be decided easily by displaying an estimation signal and a measured signal at a time.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a continuation of application Ser. No. 09/900,144 filed 9 Jul.2001, now U.S. Pat. No. 7,286,870 allowed, which is a continuation ofapplication Ser. No. 09/203,610 filed 2 Dec. 1998, now U.S. Pat. No.6,282,438 B1, which is a continuation of application Ser. No. 09/149,155filed 8 Sep. 1998, now U.S. Pat. No. 6,128,517 A, which is acontinuation of application Ser. No. 08/539,871 filed 6 Oct. 1995, nowU.S. Pat. No. 5,803,909 A, the disclosures of all of which areincorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

The present invention relates to a living body optical measurementsystem and an imaging method in the system and more particularly, to aliving body optical measurement system and an imaging method which areadapted to measure in vivo information by using light and to imageresults of measurement.

Desired in clinical medical treatment is a system or a method formeasuring the interior of a living body with ease without adverselyaffecting the living body. Measurement using light is very effective tothe desirability. The first reason for this is that the oxygen metabolicfunction inside the living body corresponds to the concentration of aspecified pigment (hemoglobin, cytochrome aa3, myoglobin or the like) inthe living body, that is, the concentration of a light absorber and theconcentration of the specified pigment can be determined from anabsorption amount for light (having wavelengths of from visible rays tonear infrared rays). The second reason is that light can be handledeasily by optical fibers. The third reason is that optical measurementdoes not harm the living body when used within the safety standards.

A system which utilizes the advantages of the living body measurementbased on light to irradiate light having wavelengths of from visiblerays to near infrared rays on a living body and measure the interior ofthe living body from reflection light at a location about 10 to 50 mmdistant from an irradiation position is described in, for example,patent disclosures of JP-A-63-277038 and JP-A-5-300887. Also, a systemfor measuring CT images of the oxygen metabolic function from lighttransmitting through a living body having a thickness of 100 to 200 mm,that is, an optical CT system is described in, for example, patentdisclosures of JP-A-60-72542 and JP-A-62-231625.

Known as a conventional living body optical measurement system is anoximeter for measuring the degree of oxygen saturation in the artery(JP-A-55-24004). The oximeter is a system in which light having aplurality of wavelengths is irradiated on a living body, thetransmitting light intensity or reflection light intensity from theliving body is measured, and spectroscopic characteristics of reducedhemoglobin (Hb) and hemoglobin oxide (HbO2) and pulsation waves areutilized to calculate the degree of oxygen saturation in the artery.

Also known as a method for measuring the degree of oxygen saturation intissues of a living body (average degree of oxygen saturation in boththe artery system and the vein system) and the hemodynamic amount is amethod by Jöbsus et al (JP-A-57-115232). This method utilizesspectroscopic characteristics of Hb and HbO2 to measure the degree ofoxygen saturation and the hemodynamic amount in tissues of a livingbody.

To add, in the present specification, transmitting light, reflectionlight and scattering light are not particularly discriminated from eachother and the intensity of light which is emitted from a light source,interacts with a living body and then is detected by a photodetector iscalled the transmitting light intensity.

Problems that the invention is to solve are three as below.

(First Problem)

In order to analyze the function of a living body, a change inhemodynamic movement due to loading is sometimes measured from thedifference between the hemodynamic movement when a load is applied tothe living body and the change in hemodynamic movement during unloading.

The hemodynamic movement during unloading is not always constant butchanges with time. As an example, a time-variable change in transmittinglight intensity is shown in FIG. 1 which is obtained when light isirradiated on a temporal of a subject who lies quietly on his or herback and the transmitting light intensity is measured at a point 3 cmdistant from a light irradiation position. As illustrated in FIG. 1,while fluctuation in the measuring system is only about 0.3%, the livingbody transmitting light intensity changes irregularly and greatly as awhole while exhibiting periodical change components. The fluctuation intransmitting light intensity is attributable to a change in thehemodynamic movement in the living body.

Even when the subject keeps quiet, the irregular change occurs in thetransmitting light intensity signal in this manner and consequently,when the transmitting light intensity upon start of measurement istreated as a reference value, change in hemodynamic movement due to loadis difficult to separate from the measured signal. Further, this causesthe observer to be prevented from deciding whether a time-variablechange in a measured signal displayed on a display unit or atime-variable change in hemodynamic movement calculated from themeasured signal is due to fluctuation owned by the living body or is dueto the application of a load. Accordingly, in the prior arts, thetransmitting light intensity upon start of measurement is treated as thereference value and therefore, there arises a problem that the subjectmust be kept to be quiet to maintain the reference value and themeasurement cannot be proceeded with for a long period of time until thesignal becomes stable.

(Second Problem)

It has hitherto been known to optically measure the cerebral cortexunder the skull with an optical spot by means of a light generating andreceiving element and a fiber, but measurement of an image of ahemodynamic state covered with the protective tissues such as skintissues and bone tissues, that is, measurement with a plurality ofmeasuring points, has been neither disclosed nor suggested. For example,when oxygen metabolism changes locally, it has been difficult to detectwhere the change occurs.

For extraction of light signals, the measuring time, i.e., the number ofintegral operations of measurement must be increased. As a result, themeasuring time is prolonged and not only a mental burden is imposed onthe subject but also the operation efficiency of the system is degraded.

The present invention intends to solve the prior art problems as above.

(Third Problem)

With the prior arts, the degree of oxygen saturation in the artery orthe hemodynamic movement in the living body tissues can be measured.But, the prior arts cannot discriminate an change in hemodynamicmovement due to an overall change in the living body from a change inhemodynamic movement due to a local change in the living body.

On the other hand, only the change in hemo-dynamic movement due to thelocal change in the living body is sometimes desired to be detected.

For example, in the cerebrum of the living body, a local portion existswhich acts in correspondence to each function of the living body(hereinafter referred to as a functional portion) and the hemodynamicamount or the degree of oxygen saturation at the functional portion ofthe cerebrum changes locally in correspondence to an arbitrary functionof the living body. At that time, if a change in hemodynamic amount orin degree of oxygen saturation at only the arbitrary functional portioncan be measured locally, then the action of the cerebral functionalportion can be examined in detail, contributing to a great importancefrom the standpoint of medical science.

For example, the signal representative of fluctuation in transmittinglight intensity in FIG. 1 is difficult to discriminate because anoverall hemodynamic movement signal in the living body is accompanied byfluctuation and even when only the local hemodynamic movement changes, asignal indicative of the change is buried in the fluctuation.

SUMMARY OF THE INVENTION

An object of the present invention is to solve the above problems and torealize a living body optical measurement system which images a state ofa function of the living body by using simplified detectors throughmeasurement within a short period of time and a method for imagingresults of measurement by using the system.

Another object of the present invention is to perform measurement whichis difficult to achieve with the prior arts and in which a local changein hemodynamic movement is measured separately and discriminatively froman overall change in hemodynamic movement in the living body.

(For the First Problem)

When a change in hemodynamic movement due to load is measured,measurement is carried out by alternately providing time during whichthe load is not applied to a living body (unloading time) and timeduring which the load is applied to the living body (loading time).Here, where a signal measured by the living body optical measurementsystem (measured signal) is Sm(t), a signal due to a change inhemodynamic movement during unloading (non-load signal) is Str(t), and asignal due to a change in hemodynamic movement during loading (loadsignal) is Sl(t), the measured signal Sm(t) is given by the followingequation (1):Sm(t)=Str(t)+Sl(t)   (1),t being the measuring time.

In the present invention, a signal during the non-load time is extractedfrom the measured signal Sm(t) to predict the function Str(t) indicativeof the non-load signal (estimated non-load signal) and the load signalSl(t) is determined from the difference between the measured signalSm(t) and the estimated non-load signal Str(t). Further, by displayingthe determined measured signal and the predicted non-load signal at atime, thus making it easy to decide whether fluctuation in the measuredsignal is due to fluctuation in the load or due to fluctuationattributable to the living body during unloading.

Determination of the function Str(t) can be effected by inputting anarbitrary function having indefinite coefficients into a computerthrough, for example, a keyboard and determining the indefinitecoefficients by, for example, the method of least squares such that thefunction fits optimally to the non-load signal. The load signal Sl(t)does not fall to zero as soon as the load is removed from the livingbody and therefore, by setting the predetermined relaxation timefollowing the loading time and determining the function Str(t) by usingthe measuring time corresponding to the unloading time exclusive of therelaxation time, a more accurate function Str(t) can be determined.

The above function Str(t) can be determined such that a single functioncan cover a plurality of load times, for example, the entire measuringtime or can be determined every load time so as to cover only therespective load times. With a method of determining functions St(t) forthe respective load times by using measured signals Sm(t) obtainedbefore and after each load time, high estimated accuracy can beobtained.

(For the Second Problem)

To achieve the above object, a living body optical measurement systemaccording to the present invention comprises a plurality of lightirradiation units for irradiating light rays having the wavelength rangeof from visible rays to near infrared rays on a subject, a plurality oflight receiving units for detecting light rays irradiated from the lightirradiation units and transmitting through the interior of the subject,a memory for storing, in time sequence, signals detected by the lightreceiving units and delivered out of the respective ones of theplurality of light receiving units, an arithmetic unit for performingconversion into signals of measured objects at a plurality of measuringpoints by using the signals stored in the memory, and an imagepreparation unit for determining a signal at a measuring position fromthe output of the arithmetic unit is measured presumptively anddisplaying the determined signal as an image indicative of an intensitysignal on a two-dimensional display screen. In particular, each of theplurality of light irradiation units includes a plurality of lightsources having different wavelengths, modulators for modulating thelight rays of the plurality of light sources with different frequencies,and wave guides for guiding a plurality of modulated light rays to theirradiation positions, and each of the plurality of light receivingunits includes a splitter for splitting the intensity of light from eachof the plurality of light sources having the different wavelengths.

The presumptive measuring position location is intermediate between thelight irradiation unit and the light receiving unit and morespecifically, the exact presumptive measuring position is anintermediate portion between a living body surface position irradiatedwith the light form the light irradiation unit and a light receivingsurface position of the living body. Here, however, the lightirradiation unit is close to the light receiving unit and therefore, itis not particularly problematic that the presumptive measuring positioncan be replaced with substantial half the distance between the center ofthe light irradiation unit and the light receiving unit. Further, in onemethod for determination of the intermediate position, light from thelight irradiation unit is irradiated on the living body and signals aredetected by two light receiving units disposed at sites which aresymmetrical to the light irradiation unit. The difference signal betweenthese signals is produced and an intermediate location between the lightreceiving unit location and the light irradiation unit which is obtainedby positioning the light receiving units through such an adjustment ofthe two light receiving units that the difference signal is rendered tobe zero level.

To make up the above description, when the function of the interior of aliving body is measured using the above living body optical measurementsystem, light irradiation positions of the plurality of lightirradiation means are distributively arranged on a measuring portion ofa subject, a plurality of light receiving portions of the plurality oflight receiving means are disposed around the distributively arrangedlight irradiation positions, respectively, and for light signalsdetected by the plurality of light receiving means, a position on aperpendicular vertical to the living body surface, which position is anintermediate point between the light irradiation position and the lightdetection position and extending to the interior of the living body isset as a presumptive measuring point. The signal at the presumptivemeasuring point is calculated by the light signal detected by the plurallight receiving means. This is because according to spatialcharacteristics of light density irradiated from the light irradiationposition and then reaching the detection position, the density is highimmediately below the irradiation position and the detection positionnear the surface by virtue of scattering of light from the surface butwhen an arbitrary depth determined by the distance between lightirradiation position and detection position and the light scatteringcharacteristics of the living body is exceeded, the density becomes thehighest even at an intermediate location between the irradiationposition and the detection position and eventually, the sensitivitybecomes the highest at the intermediate location. Light signal intensitydetected in correspondence to the aforementioned presumptive measuringpoint and measuring point is displayed on a two-dimensional image. Whenthe light signal intensity is desired to be displayed as a topographyimage, signals at unmeasured locations can be obtained in the form ofinterpolated signals associated with the aforementioned presumptivemeasuring points.

When the above subject is a living body, the distance between theirradiation position and the detection position is preferably 10 to 50mm. Here, determination of the factor for determining the maximumdistance has relation to the intensity of irradiated light andattenuation in the living body.

(For the Third Problem)

Advantageously, in the present invention, light rays are irradiated froma desired single site or a plurality of sites on a living body, twosites of a detection position at which a local change is measured as achange in signal and a detection position at which a local change is notmeasured as a change in signal are set to be substantially equidistantfrom a light irradiation position, transmitting light intensity levelsare detected at the respective detection positions, and the differencebetween transmitting light intensity levels at the two sites isproduced, so that a fluctuation component in the living body common tothe two detection positions can be removed to permit a slight change inone of the light receiving units to be detected with high sensitivity.When the aforementioned two sites of detection position cannot be found,the light irradiation position is displaced to find the detectionpositions. Namely, like a stethoscope, wanted measuring positions can besearched.

Preferably, transmitting light rays are received at two sites ofdetection positions equidistant from the incident position anddifferently positioned, transmitting light intensity levels at therespective detection positions are converted into electric signals byusing photoelectric conversion elements such as photodiodes orphotomultiplier tubes (hereinafter, electric signals meaning thetransmitting light intensities will be referred to as transmitting lightintensity signals), the individual transmitting light signal intensitylevels are subjected to logarithmic conversion by means of logarithmicamplifiers, and a transmitting light intensity signal at the firstdetection position and a transmitting light intensity signal at thesecond detection position are then amplified and detected bydifferential amplifiers.

By modulating light emitted from the light source in intensity andextracting only a frequency component for intensity modulation of adetected signal, noises due to external disturbance can be removed.

The light source can be connected to the light irradiation positionthrough an optical fiber and the light detection position can beconnected to the photodetector through an optical fiber.

Since, in the present invention, information about a measuring positioncan be determined substantially definitely by the position at whichlight is irradiated on a subject by the light irradiation means and theposition of the light receiving means, the signal processing fordisplaying the information as an image can be conducted easily at a highspeed. Also, with the light receiving means disposed about 10 to 50 mmclosely to the light irradiation position, transmitting light isutilized to obtain the detection intensity which is sufficiently high,amounting to about 6 order or more higher than light transmittingthrough a living body of about 100 to 200 mm. Therefore, measurement canbe carried out with simplified photodetectors and can be completedwithin a short period of time.

For example, when the object to be measure (subject) is the head, it isknown as reported in, for example, “Intracerebral penetration ofinfrared light” by Patric W. McCormic el al, Journal of Neurosurgerypublished in February, 1992, Vol.76, paragraphs 315-318) that for thedistance between the irradiation position and the detection positionbeing at least 30 mm, detection light transmits through the skin andskull to reach the surface portion of the cerebrum, i.e., the cerebralcortex. It is also known from characteristics of light propagation inthe living body that information from a location which lies on aperpendicular vertical to the surface of the living body and extendingto the interior of the living body from an intermediate point betweenthe irradiation and detection positions is contained most richly inlight detected at that detection position. Such characteristics arereported in, for example, “Monte Carlo simulation of photon pathdistribution in multiple scattering media” by Shecha Feng et al, SPIE,Proceedings of photon migration and imaging in random media and tissues,Vol. 1888, paragraphs 78-89, (1993).

The living body optical measurement system of the present inventionneeds a number of light irradiation means and a number of lightreceiving means for measurement at many positions but as will bedescribed in embodiments to be described later, the system is effectiveto measurement at a partial position and images can be obtained througha simplified arithmetic processing in which measurement results obtainedat a plurality of measuring points are interpolated in association withthe respective measuring points.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing fluctuation in living body transmitting lightintensity obtained with a conventional system.

FIG. 2 is a block diagram showing the construction of an embodiment of aliving body optical measurement system according to the presentinvention.

FIG. 3 is a diagram for explaining an embodiment of an imaging methodusing the measuring system of FIG. 2.

FIG. 4 is a graph depicting a time-variable change in measured signal ata measuring point in the above embodiment and a time-variable change inestimated non-load signal 15 determined from the measured signal.

FIG. 5 is a graph depicting a time-variable change in relative changeamount of hemoglobin concentration at a measuring point in the aboveembodiment.

FIG. 6 is a graph depicting a topography image in the above embodiment.

FIG. 7 is a graph depicting another example of the topography image inthe above embodiment.

FIG. 8 is a graph depicting an example of display of topography image inthe above embodiment.

FIG. 9 is a diagram for explaining a method for coordinate conversion inanother embodiment of the living body optical measurement system of thepresent invention.

FIG. 10 is a graph showing an example of display in the measuring systemof the present invention.

FIGS. 11A and 11B are graphs showing examples of display according tothe measuring system of the present invention.

FIGS. 12A and 12B are graphs showing examples of display according tothe measuring system of the present invention.

FIG. 13 is a graph showing an example of display according to themeasuring system of the present invention.

FIG. 14 is a graph showing an example of display according to themeasuring system of the present invention.

FIG. 15 is a block diagram for explaining the construction of a systemaccording to another embodiment of the present invention.

FIG. 16 is a block diagram for explaining the construction of a systemaccording to another embodiment of the present invention.

FIGS. 17A and 17B are schematic sectional and bottom views of a lightdetection probe in another embodiment of the present invention.

FIG. 18 is a schematic bottom view showing another embodiment of thelight detection probe.

FIG. 19 is a schematic diagram for explaining an example of use of thelight detection probe.

FIG. 20 is a block for explaining the construction of a system accordingto another embodiment of the present invention.

FIG. 21 is a block for explaining the construction of a system accordingto another embodiment of the present invention.

FIG. 22 is block for explaining the construction of a system accordingto another embodiment of the present invention.

FIG. 23 is a block for explaining the construction of a system accordingto another embodiment of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Embodiment 1

Embodiments of the present invention will be described hereinafter.

FIG. 2 shows the construction of an embodiment of a living body opticalmeasurement system according to the present invention. The presentembodiment is an example in which the living body optical measurementsystem is applied to the measurement of a change in hemodynamic movementattributable to a cerebral function (a relative change amount ofconcentration of hemoglobin oxide and reduced hemoglobin). A specifiedportion of the cerebrum is related to control of an in vivo specifiedfunction (for example, moving a part of a body such as fingers) and thehemodynamic movement at the specified cerebral portion is changed byactivating the specified function. In one form of the presentembodiment, the living body optical measurement system can also be usedto measure changes in hemodynamic movement under the application of aload for activation of the aforementioned specified function, forexample, moving fingers and display measured changes in the form of acontour map on a two-dimensional plane image indicative of the cerebralportion.

As shown in FIG. 2, there are provided in the present embodiment aplurality of light sources 2 a to 2 d having different wavelengths (thelight sources 2 a, 2 c and the light sources 2 b, 2 d having the samewavelengths, respectively, which are in the range of from visible raysto near infrared rays), modulators for modulating the intensity of lightrays of the plurality of light sources 2 a and 2 b (2 c and 2 c) bymeans of oscillators 1 a and 1 b (1 c and 1 d) having mutually differentfrequencies, a plurality of light irradiation means for irradiatinglight rays from couplers 4 a (4 b), adapted to couple anintensity-modulated light ray propagating through an optical fiber 3 a(3 c) and that propagating through an optical fiber 3 b (3 d), ontodifferent positions on the scalp of a subject 6 standing for an objectto be examined through the medium of optical fibers 5 a (5 b), and aplurality of light receiving means comprised of photodetectors 8 a to 8f provided for a plurality of optical fibers 7 a to 7 d for lightdetection and a plurality of light detection optical fibers 7 e and 7 fhaving their tip ends positioned near the light irradiation positions ofthe plurality of light irradiation means at locations equidistant(assumed herein to be 30 mm) from the light irradiation positions.Living body transmitting light rays are collected to optical fibers bymeans of the six light detection optical fibers 7 a to 7 f and arephotoelectrically converted by the photodetectors 8 a to 8 f,respectively. The light receiving means is operable to detect andconvert light reflected inside the subject into an electric signal and aphotoelectric conversion element represented by a photomultiplier tubeor a photodiode is used as the photodetector 8.

Electric signals indicative of the living body transmitting lightintensity levels which are photoelectrically converted by thephotodetectors 8 a to 8 f (hereinafter referred to as living bodytransmitting light intensity signals) are inputted to lock-in amplifiers9 a to 9 h, respectively. Since the photodetectors 8 c and 8 d detectsliving body transmitting light intensity levels collected by the lightdetection optical fibers 7 c and 7 d which are equidistant from both ofthe optical fibers 5 a and 5 b, signals from the photodetectors 8 c and8 d are split into two systems so as to be inputted to the lock-inamplifiers 9 c and 9 e and the lock-in amplifiers 9 d and 9 f. Theintensity modulation frequencies from the oscillators 1 a and 1 b areinputted, as reference frequencies, to the lock-in amplifiers 9 a to 9 dand the intensity modulation frequencies from the oscillators 1 c and 1d are inputted, as reference frequencies, to the lock-in amplifiers 9 eto 9 h. Accordingly, living body transmitting light intensity signalsassociated with the light sources 2 a and 2 b are separately deliveredout of the lock-in amplifiers 9 a to 9 d and living body transmittinglight intensity signals associated with the light sources 2 c and 2 dare separately delivered out of the lock-in amplifiers 9 e to 9 h.

Exemplarily, for contour map display, the separated transmitting lightintensity signals of individual wavelengths delivered out of the lock-inamplifiers 9 e to 9 h are subjected to analog to digital conversion byan analog to digital converter 10 and are then stored in a memory 12provided internally or externally of a computer 11. During or aftermeasurement, the computer 11 uses the transmitting light intensitysignals stored in the memory to calculate relative change amounts ofconcentration values of hemoglobin oxide and reduced hemoglobin whichare to be determined from detection signals at individual detectionpoints and stores the calculated amounts in the memory 12 astime-variable information at a plurality of measuring points m. Theabove calculation will be described later in greater detail. A displaycontroller 30 converts the signals stored in the memory means 12 intodisplay signals for a display unit 13 such as a CRT and displays them onthe display unit 13. In the display signals, measuring positions areconverted into coordinates on the display plane of the subject andtreated as signals for intensity signal (relative change amounts ofconcentration values of hemoglobin oxide and reduced hemoglobin) contourmap display at the coordinate positions.

By using the living body optical measurement system according to thepresent embodiment, relative change amounts of concentration values ofhemoglobin oxide and reduced hemoglobin in the living body can bemeasured easily at a high speed. The expanded construction in which thenumber of light incident points (light irradiation positions) and thenumber of light detection points are increased can be feasible with easeby increasing the number of intensity modulation frequencies of thelight sources, of the light sources, of the photodetectors and of thelock-in amplifiers. With the present living body optical measurementsystem used, the spectroscopic positions and the light irradiationpositions can be separated in accordance with the intensity modulationfrequencies and therefore, even when the number of the light irradiationpositions is increased, it suffices that the number of wavelengths ofirradiation light rays at the respective light irradiation positionsequals the number of absorbers to be measured, and the wavelength of anirradiation light ray need not particularly be changed for therespective light irradiation positions. Accordingly, the number ofwavelengths of irradiation light rays used is small and an error due tothe influence of scattering which changes with the wavelength can bedecreased.

FIG. 3 is a diagram for explaining an embodiment of an imaging methodaccording to the present invention which uses the living body opticalmeasurement system, showing the relation among the light incident point,the light detection point and the measuring point in the above method.The imaging method of the present embodiment is a method for preparingimages of relative change amounts of concentration values of hemoglobinoxide and reduced hemoglobin at the head of a subject, wherein fourincident points and four detection points are provided at the lefttemporal participating in the motion function of right fingers of thesubject so as to measure living body transmitting light intensity levelsand results of measurement obtained under the application of a load ofright-finger motion and a load of left-finger motion are imaged.

As shown in FIG. 3, light incident points 17 a to 17 d and detectionpoints 18 a to 18 d are disposed on the left temporal of a subject 16.Here, the respective light incident points are in correspondencerelationship with the respective detection points through tens sets of17 a-18 a, 17 a-18 b, 17 b-18 a, 17 b-18 b, 17 b-18 c, 17 b-18 d, 17c-18 b, 17 c-18 c, 17 d-18 c and 17 d-18 d. The distance between thecorresponding light incident point and detection point is 30 mm.Further, as described in the previously-described “Monte Carlosimulations of photon path distribution in multiple scattering media” byShechao Feng et al, time-variable changes in the relative change amountsof concentration values of hemoglobin oxide and reduced hemoglobin to bedetermined from measured signals at the respective detection points bestreflect information from an intermediate point between the correspondingincident point and detection point and hence, presumptive measuringpoints 19 a to 19 j are each set in the middle of the correspondencerelation between each incident point and each detection point.Information at the presumptive measuring points 19 a to 19 j isdetermined and the magnitude of the information is displayed in the formof a contour map, a light and shade map or a color discrimination map onthe two-dimensional plane as shown in FIG. 3.

Next, there will be described an embodiment of a method according to thepresent invention for determining relative change amounts ofconcentration values of hemoglobin, that is, changes in concentrationvalues of hemoglobin at a specified cerebral portion obtained when aspecified in vivo function (for example, moving a part of body such asfingers) is activated, from measured signals at the respective lightdetection points.

FIG. 4 is a graph illustrating a measured signal 14 at one of thedetection points 18 a to 18 d of the living body optical measurementsystem and a time-variable change in estimated non-load signal 15determined from the measured signal 14 in the embodiment of FIG. 3. Inthe graph, abscissa represents measuring time and ordinate representsrelative concentration change amount.

The estimated non-load signal 15 is determined by removing from themeasured signal 14 signals occurring during time Tt for a load to beapplied (loading time) and during time T2 for the signal to recover itsintact form following loading (relaxation time) and fitting an arbitraryfunction to the measured signal 14 occurring during load preceding timeT1 and load succeeding time T3 through the use of the method of leastsquares. The present embodiment is handled by using a quadratic linearpolynomial as the arbitrary function and setting respective times toT1=40 seconds, T2=30 seconds, Tt=30 seconds and T3=30 seconds.

FIG. 5 is a graph illustrating time-variable changes in relative changeamounts of concentration values of hemoglobin oxide and reducedhemoglobin (hereinafter represented by ΔCoxy(t) signal 20 and ΔCdeoxy(t)signal 21, respectively) at one measuring point. In the graph, abscissarepresents measuring time and ordinate represents relative concentrationchange amounts. A hatched time interval corresponds to load applyingtime (motion period of right fingers). From the measured signal 14 andestimated non-load signal 15 of two wavelengths indicated in FIG. 4, theabove relative change amounts of concentration value of hemoglobin oxideand reduced hemoglobin (HbO2, Hb) under the application of a load aredetermined through the following arithmetic operation processing.

For a wavelength λ, the relation between estimated non-load signalStr(λ, t) and light source intensity I0(λ) is given by the followingequation (2) by separating in vivo light attenuation into scattering andabsorption:−Ln{Str(λ, t)/I0(λ)}=∈oxy(λ).Coxy(t).d+∈deoxy(λ).Cdeoxy(t).d+A(λ)+S(λ)  (2)where

-   -   ∈oxy(λ): extinction coefficient of hemoglobin oxide at        wavelength λ    -   ∈deoxy(λ): extinction coefficient of reduced hemoglobin at        wavelength λ    -   A(λ): attenuation due to absorption by other substances than        hemoglobin at wavelength λ    -   S(λ): attenuation due to scattering at wavelength λ    -   Coxy(t): concentration of hemoglobin oxide at measuring time t    -   Cdeoxy: concentration of reduced hemoglobin at measuring time t    -   d: in vivo effective optical path length (in a region of        interest)

Also, the relation between measured signal Sm(λ, t) and light sourceintensity I0(λ) is given by the following equation (3):

$\begin{matrix}\begin{matrix}{{{- {Ln}}\left\{ {{{{Sm}\left( {\lambda,t} \right)}/I}\; 0(\lambda)} \right\}} = {\in {{{oxy}(\lambda)} \cdot \left\{ {{C\;{{oxy}(t)}} + {C^{\prime}{{oxy}(t)}} +} \right.}}} \\{{{\left. {{N{oxy}}(t)} \right\} \cdot d} +} \in {{{deoxy}(\lambda)} \cdot \left\{ {{{C{deoxy}}(t)} +} \right.}} \\{{\left. {{C^{\prime}{{deoxy}(t)}} + {{N{deoxy}}(t)}} \right\} \cdot d} +} \\{{A^{\prime}(\lambda)} + {S^{\prime}(\lambda)}}\end{matrix} & (3)\end{matrix}$where

-   -   C′oxy(t): change in concentration of hemoglobin oxide under the        application of load at measuring time t    -   C′deoxy(t): change in concentration of reduced hemoglobin under        the application of load at measuring time t    -   Noxy(t): noise or high frequency fluctuation in concentration of        hemoglobin oxide at measuring time t    -   Ndeoxy(t): noise or high frequency fluctuation in concentration        of reduced hemoglobin at measuring time t        Here, if A(λ) and S(λ) remain unchanged under loading and        unloading, that is, if a change in the measured signal under the        application of load is due to only changes in concentration        values of hemoglobin oxide and reduced hemoglobin, the        difference between equations (2) and (3) is given by the        following equation (4):

$\begin{matrix}\begin{matrix}{{{Ln}\left\{ {{{Str}\left( {\lambda,t} \right)}/{{Sm}\left( {\lambda,t} \right)}} \right\}} = {\in {{{{oxy}(\lambda)}\left\{ {{C^{\prime}{{oxy}(t)}} + {{N{oxy}}(t)}} \right\} d} +}}} \\{\in {{{deoxy}(\lambda)}\left\{ {{C^{\prime}{{deoxy}(t)}} + {{Ndeoxy}(t)}} \right\} d}}\end{matrix} & (4)\end{matrix}$

Here, time-variable changes in relative change amounts of concentrationvalues of hemoglobin oxide and reduced hemoglobin under the applicationof load are represented by ΔCoxy(t) and ΔCdeoxy(t) and defined by thefollowing equation:ΔCoxy(t)={C′oxy(t)+Nox(t)}dΔCdeoxy(t)={C′deoxy(t)+Ndeoxy(t)}d   (5)

Usually, it is difficult to specify d and therefore, the dimension ofthe concentration change amount is herein the product of concentrationand distance d.

But, in equation (5), distance d acts equally on ΔCoxy and ΔCdoxy and soequation (5) is considered as indicating relative change amounts ofhemoglobin concentration values. When two wavelengths are used formeasurement, obtained equation (4) is reduced to a simultaneous equationwith two unknowns for ΔCoxy(t) and ΔCdeoxy(t), so that ΔCoxy(t) andΔCdeoxy(t) can be determined from estimated non-load signal Str(λ, t)and measured signal Sm(λ, t) for each wavelength. Further, what isindicated by ΔCoxy(t) and ΔCdeoxy(t) during a period other than loadingtime and relaxation time can be formulated by C′oxy(t)=0 andC′deoxy(t)=0, which indicate noises or high frequency fluctuations,attributable to the living body, of concentration of hemoglobin oxideand reduced hemoglobin. The above procedure is carried out for 0 to 140seconds to obtain ΔCoxy(t) signal 20 and ΔCdeoxy(t) signal 21 of FIG. 5.

FIGS. 6 and 7 show contour map images (topographic images) prepared fromtime-variable changes in relative change amounts of concentration valuesof hemoglobin oxide at the respective measuring points under theapplication of loads of left-finger motion and right-finger motion of asubject, respectively. A method for preparation of the topography imagesis such that a time integral (alternatively, time average) of relativechange amount ΔCoxy(t) signal 20 during load applying time (hatchedperiod in FIG. 5) is calculated by the computer 11 and values betweenindividual measuring points are determined through linear interpolationin X-axis and Y-axis directions. In addition to the contour map, thetopographic image may include a monochromatic light and shade image anda discrimination display in color. It will be seen by comparing theimages of FIGS. 6 and 7 that the concentration of hemoglobin oxideclearly increases at specified positions during the right hand motion.By displaying this type of spatial distribution information as images,rapid and easy recognition of measurement results can be ensured. Whilethe images shown in FIGS. 6 and 7 are prepared from the time integralvalues of concentration relative change amounts during the load applyingtime, a topography image can also be prepared similarly from relativechange amounts of concentration values of hemoglobin oxide which aremeasured every constant measuring time at the respective measuringpoints. When a plurality of topographic images thus prepared inaccordance with order of the measuring time points or displayed as amoving picture, time-variable changes in the relative change amounts ofconcentration values of hemoglobin oxide can be obtained.

Further, by calculating time-variable changes in relative change amountsof concentration values of hemoglobin oxide at an arbitrary measuringpoint as well as a self correlation function and a mutual correlationfunction of time-variable changes in relative change amounts ofconcentration values of hemoglobin oxide at that arbitrary measuringpoint and another measuring point, a topographic image can be preparedfrom the correlation functions at the individual measuring points. Thecorrelation function at each measuring point is a function defined bytime shift τ and therefore, by preparing topography from a value of thecorrelation function at the same time shift τ and displaying thetopography in accordance with order of τ or displaying it in the form ofa moving picture, hemodynamic movement which changes by participating inactivation of the cerebral function can be visualized.

Here, the relative change amount of concentration of hemoglobin oxide istypically used for explanation but the relative change amount ofconcentration of reduced hemoglobin or the total hemoglobinconcentration change amount which is calculated by adding the relativechange amount of concentration of hemoglobin oxide and the relativechange amount of concentration of reduced hemoglobin may be used toprepare topographic in a similar way.

FIG. 8 shows a display example in which a topography image 22 preparedthrough the above-described method is superimposed on a cerebral surfaceimage 23. Since the topographic image 22 is illustrative of a change incerebral hemodynamic movement which changes in association with anbiological function, it is preferably displayed while being superimposedon the cerebral surface image. The cerebral surface image 23 is measuredthrough three-dimensional MRI or three-dimensional X-ray CT and isdisplayed. The topographic image 22 is subjected to coordinateconversion such that coordinates of individual measuring points arepositioned on the cerebral surface and values between individualmeasuring points subject to the coordinate conversion are interpolatedto prepare the topographic image. When the prepared topographic image 22is displayed while being superimposed on the cerebral surface image 23,color of the overlying topographic image 22 is made to besemitransparent to allow the underlying cerebral surface image to beseen transparently.

FIG. 9 shows a diagram for explaining a measuring point coordinateconverting method. A method of taking images of the form ofthree-dimensional MRI or three-dimensional X-ray CT will hereunder bedescribed specifically. In FIG. 9, 5 a designates an optical fiber forirradiation and 7 a an optical fiber for detection. Information at aportion on the center line between these fibers is presumed for use asinformation at a desired measuring point. This is because a portion isused at which the supply of the quantity of light from the irradiationfiber is maximized and the signal from an object to be measured ismaximized. By performing imaging while disposing a marker at themeasuring point 29 which is presumptively set by the living body opticalmeasurement system, a skin and skeleton image 24, a cerebral image 25and a marker image 26 can be displayed on the basis of the imaged forminformation. The images picked up as above have three-dimensionalcoordinate information. Thus, a perpendicular 28 passing through ameasuring point 27 indicated by the marker image 26 and being verticalto the skin surface at the measuring point 27 or the bottom of themarker image 26 is calculated and a point at which the perpendicularintersects the cerebral image 25 is defined as the measuring point 29subject to the coordinate conversion. As shown in the presentembodiment, it is known that when the cerebral function is measured, achange in hemodynamic movement having correlation to load occurs mainlyat the cerebral surface (cerebral cortex). For the reasons set forth asabove, by using anatomical information, the depth for coordinateconversion of measuring points can be known. But when an object to bemeasured is another living body organ such as muscles, the depth forcoordinate conversion of measuring points cannot sometimes be known fromthe anatomical information. In applying the present method to themeasurement as above, light propagation of living tissue is calculatedin advance through numerical calculation based on the Monte Carlo methodto determine a depth best contributing to measured signals andcoordinates of the measuring point are converted to the thus determineddepth.

The topographic image has been described as presumptive display imagebut a different image display method is available.

For example, a square pixel of arbitrary size having the center ofgravity at a presumptive measuring point is set at each presumptivemeasuring point, each pixel is displayed either in the form of an imagein light and shade painted in color in correspondence to a value of eachpresumptive measuring point, the correspondence being determined inadvance, or in the form of a bar graph image indicated by a bar or alength of line which corresponds to a value of each measuring point.

In all image display methods, color arrangement can be selected freelywhen color is used but for measurement of hemodynamic movement, displayin combination of light and shade of red color and light and shade ofblue color is preferable. This is because such an image that arterialhemodynamic is red and venous hemodynamic is blue is fixed. For example,the magnitude of positive measured value is displayed in light and shadeof red color and the magnitude of negative measured value is displayedin light and shade of blue color.

Embodiment 2

A second embodiment according to the present invention will bedescribed.

FIG. 10 shows an example of display of measured signals and estimatednon-load signals. Displayed measured signals 110 a and 110 b are outputsignals from the lock-in amplifier 9 a and estimated non-load signals111 a and 111 b are calculated from the respective measured signals(calculation method will be described later).

The estimated non-load signals 111 a and 111 b are displayed on thedisplay unit. In the displayed graph, abscissa represents measuring timeand ordinate represents relative values of measured signals indicativeof transmitting light intensity levels measured by the living bodyoptical measurement system.

When a load is applied to a subject, a loading start mark 112 indicativeof a load application starting time point and a loading end mark 113indicative of a load application ending time point are displayed in theform of straight lines. In the present embodiment, the cerebral cortexregion dominating the right-hand motion is measured from the scalpthrough the skull and the right-hand or left-hand motion is applied as aload (loads 1 and 3 correspond to the right-hand motion and loads 2 and4 correspond to the left-hand motion). Although in FIG. 10 all signalsoccurring throughout the measuring time, only a desired time interval(for example, a time interval including times before and after theloading time) can be displayed easily. Also, if the estimated non-loadsignals 111 a and 111 b are each displayed until a desired time point onan extension of the curve indicative of a time-variable change, themeasured signals 110 a and 110 b and the estimated non-load signals 111a and 111 b can be displayed simultaneously on real time base duringmeasurement. By simultaneously displaying the measured signals 110 a and110 b and the estimated non-load signals 111 a and 111 b in this manner,a change in hemodynamic movement occurring in the living body can bedecided easily by an observer. The estimated non-load signals displayedin advance on real time base can be corrected for display in the phaseat which calculation of the estimated non-load signals is settled.

The estimated non-load signals 111 a and 111 b can be determined byremoving signals occurring during the load applying time (loading time)and signals occurring during the time for the signal to recover itsintact form following removal of the load (relaxation time) and byfitting an arbitrary function to signals occurring during the remainingperiod through the method of least squares. Here, the arbitrary functionand the relaxation time change with the kind of load and measurementlocations and so those meeting the purpose of measurement are inputtedthrough the input unit. In the present embodiment, the arbitraryfunction in the form of a polynomial of degree five is handled and therelaxation time is set to 30 seconds. Further, for the convenience ofwatching by the observer, different kinds of color or different kinds oflines can be used for display of signals.

FIGS. 11A and 11B show examples of display of a difference signalbetween a measured signal and an estimated non-load signal and in thesefigures, a waveform of a difference signal 114 a obtained by calculatingthe difference between the measured signal 110 a and the estimatednon-load signal 111 a in FIG. 10 and a waveform of a difference signal114 b obtained by calculating the difference between the measured signal110 b and the estimated non-load signal 111 b in FIG. 10 are displayedon the display unit. In the displayed graph, abscissa representsmeasuring time and ordinate represents relative difference signalintensity. Further, when a load is applied to a subject, a load startmark 112 indicative of a load application starting time point and a loadend mark 113 indicative of a load application ending time point aredisplayed in the form of straight lines. Also, the present graph is agraph having its center at 0 and so shows a base line 115.

In the present embodiment, waveforms 114 a and 114 b are displayed ondifferent coordinate axes for different light source wavelengths butthey can be displayed overlapping each other on the same coordinateaxis. Also, for the convenience of watching by an observer, differentkinds of color or different kinds of lines can be used for display.

FIGS. 12A and 12B show examples of display of graphs depicting relativechange amounts of concentration values of HbO2 and Hb (hereinafterrepresented by ΔCoxy and ΔCdeoxy, respectively) under the application ofload. A waveform of a ΔCoxy signal 116 a obtained from the measuredsignal 110 a and estimated non-load signal 111 a in FIG. 10 pursuant toequation (5) and a waveform of a ΔCdeoxy signal 116 b obtained from themeasured signal 110 b and estimated non-load signal 111 b in FIG. 10pursuant to equation (5) are displayed on the display unit. In thedisplayed graph, abscissa represents measuring time and ordinaterepresents values of ΔCoxy and ΔCdeoxy. Further, a load start mark 112,a load end mark 113 and a base line 115 are also displayed. In thepresent embodiment, all intervals of measuring time are displayed butonly desired time intervals (for example, a period including time pointsbefore and after the loading time) can be displayed. Here, the waveforms116 a and 116 b are displayed separately on different coordinate axesbut they may be displayed overlapping each other on the same coordinateaxis. Further, the individual signals may be displayed in differentkinds of color or in the form of different kinds of lines and forintuitive understanding by an observer, the ΔCoxy signal 116 a may bedisplayed in, for example, a kind of red color and the ΔCdeoxy signal116 b may be displayed in, for example, a kind of green color. Accordingto the measuring method and display method of the present invention, thecorrelation between load and measured signal is easy to understand andfluctuation is removed from the measured signal, thus ensuring thataccuracy of signals can be increased.

FIG. 13 shows an example of display of a ΔCoxy loading time integralvalue 117 a and a ΔCdeoxy loading time integral value 117 b which areobtained during respective loading times. The ΔCoxy signal 114 a and theΔCdeoxy signal 114 b in FIGS. 11A and 11B are time integrated duringeach loading time to determine the ΔCoxy loading time integral value 117a and ΔCdeoxy loading time integral value 117 b, which are displayed inthe form of a cubic bar graph for respective load number. Here, abscissarepresents load number and ordinate represents ΔCoxy loading timeintegral value and ΔCdeoxy loading time integral value. Alternatively, aΔCoxy loading time average value and a ΔCdeoxy loading time average timemay be displayed. Also, for the convenience of watching by an observer,display in different colors can be used.

FIG. 14 shows an example of display when measurement is conducted at aplurality of measuring positions by using the living body opticalmeasurement system. Here, an instance will be described where theportion to be measured is the head and four measuring positions are seton the head.

In the present display example, a measuring portion image 118 of asubject, measuring position marks 119 a to 119 d representative of setmeasuring positions, graphs 121 a to 121 d corresponding to therespective measuring positions and index lines 120 a to 120 d forindicating the correspondence relation between the respective measuringpositions and the respective graphs are displayed on the display unit.Here, a head model figure or a measuring portion tomographic image ormeasuring portion three-dimensional image of a subject itself imaged byan image diagnostic apparatus represented by an MRI apparatus can beused as the measuring portion image 118.

Embodiment 3

The schematic construction of embodiment 3 of the living body opticalmeasurement system according to the present invention is shown in FIG.15.

Light emitted from a light source 201 is collected using a lens systemso as to impinge on an optical fiber 202 for light source. The lightemitted from the light source is modulated in intensity with a desiredfrequency f of about 100 Hz to 10 MHz by means of an oscillator 223 inorder to remove noises due to external disturbance. Since the lightsource optical fiber 202 is connected to an optical fiber 204 for lightirradiation through an optical fiber coupler 203 a, the light from thelight source is transmitted to the light irradiation optical fiber 204and is irradiated on a subject 206 by way of a light irradiationposition 205. The wavelength of the light used depends on spectroscopiccharacteristics of an in vivo substance of interest but when the oxygensaturation amount and the blood amount are measured from concentrationvalues of Hb and HbO2, a single or a plurality of wavelengths can beselected, for use, from light having the wavelength range of from 600 nmto 1400 nm. A semiconductor laser, a titanium/sapphire laser or a lightemitting diode can be used as the light source.

Two light detection optical fibers 207 a and 207 b for detecting lighttransmitting through the subject 206 and going out of it are disposed attwo different sites on the subject 206. In the present embodiment, thetwo light detection optical fibers 207 a and 207 b are disposed at twosites which are point symmetrical to a symmetry center of the lightirradiation position 205. The light irradiation optical fiber 204 andthe light detection optical fibers 207 a and 207 b are held in place bymeans of an optical fiber fixing member 208 having its surface paintedin black. For simplicity of construction, the light irradiation opticalfiber 204, light detection optical fibers 207 a and 207 b and opticalfiber fixing member 208 are integrally formed into a light detectionprobe to be detailed later. Since the light detection optical fibers 207a and 207 b are connected to optical fibers 209 a and 209 b forphotodetectors through optical fiber couplers 203 b and 203 c,transmitting light rays detected by the light detection optical fibers207 a and 207 b are transmitted to photodetectors 210 a and 210 b andsubjected to photoelectric conversion by the photodetectors 210 a and210 b, so that transmitting light intensity levels are delivered in theform of electric signal intensity levels. Used as the photodetectors 210a and 210 b are photoelectric conversion elements such as for examplephotodiodes or photo-multiplier tubes.

Of electric signals indicative of transmitting light intensity levelsdelivered out of the photodetectors 210 a and 210 b, only frequencycomponents for light intensity modulation of the light source areextracted by lock-in amplifiers 224 a and 224 b, respectively. While anoutput from the lock-in amplifier 224 a is subjected to logarithmicconversion by a logarithmic amplifier 225 a and then inputted to thenegative pole of a differential amplifier 211, an output from thelock-in amplifier 224 b is subjected to logarithmic conversion by alogarithmic amplifier 225 b and subsequently inputted to the positivepole of the differential amplifier 211. As a result, a difference signalbetween transmitting light intensity levels at the two different sitesis delivered out of the differential amplifier 211 as an output signal.The output signal from the differential amplifier 211 is sequentiallyconverted into a digital signal by an A/D converter 212, fetched into acomputer 213 and displayed on a display unit 214 as time series data.

Here, when a region 215 where the hemodynamic movement changes locallyis included in only a view field 216 b of the light detection opticalfiber as shown in FIG. 15, the measured logarithmic difference signalreflects only a change in hemodynamic movement at the local region 215.On the presupposition that for near infrared rays, hemoglobin serving asa main constituent in hemodynamic dominantly acts on extinction, themeaning of the measured logarithmic difference signal will be describedbelow.

Where measuring time is t, light source wavelength is λ, irradiationlight intensity is I0(t), concentration values of hemoglobin oxide andreduced hemoglobin are Cox(t) and Cdeox(t), respectively, changes inconcentration values of hemoglobin oxide and reduced hemoglobin whichoccur at the local region 215 are ΔCox(t) and ΔCdeox(t), respectively,extinction coefficients for light source wavelength λ of hemoglobinoxide and reduced hemoglobin are ∈ox(λ) and ∈deox(λ), respectively,attenuation due to scattering and absorption caused by otherconstituents than hemoglobin is Ds and weight coefficient caused byscattering is d, transmitting light intensity signal Id(t) detected bythe photodetector 210 b is given by the following equation (6) andtransmitting light intensity signal Id′(t) detected by the photodetector210 a is given by the following equation (7):

$\begin{matrix}\begin{matrix}{{{Id}(t)} = {{Ds} \cdot {\exp\left\lbrack {- \left\lbrack {\in {{{{ox}(\lambda)}\left( {{{C{ox}}(t)} + {\Delta\;{{C{ox}}(t)}}} \right)} +}} \right.} \right.}}} \\{\left. {\in {{deox}(\lambda)\left( {{{C{deox}}(t)} + {\Delta\;{{C{deox}}(t)}}} \right)}} \right\rbrack I\; 0(t)}\end{matrix} & (6) \\\begin{matrix}{{{Id}^{\prime}(t)} = {{Ds} \cdot {\exp\left\lbrack {- \left\lbrack {\in {{{{ox}(\lambda)}{C{ox}}(t)} +}} \right.} \right.}}} \\{\left. {\left. {\in {{deox}(\lambda){{C{deox}}(t)}}} \right\rbrack d} \right\rbrack I\; 0(t)}\end{matrix} & (7)\end{matrix}$

Next, equations (6) and (7) are expressed in terms of natural logarithmand then equation (7) is subtracted from equation (6) to obtain thefollowing equation (8). The left side of equation (8) is the measuredlogarithmic difference signal.ln[Id(t)/Id′(t)]=−[∈ox(λ)ΔCox(t)+∈deox(λ)ΔCdeox(t)]d   (8)

Here, when 805 nm±10 nm is particularly used as the light sourcewavelength for measurement,∈ox(805±10)≈∈deox(805±10)   (9)stands and by using constant K, equation (8) can be reduced toln[Id(t)/Id′(t)]=−[ΔCox(t)+ΔCdeox(t)]K   (10)

Accordingly, the logarithmic difference signal measured by using thelight source wavelength 805 nm±10 nm represents a value corresponding toa change amount in hemodynamic amount [ΔCox(t)+ΔCdeox(t)](hereinafterreferred to as relative hemodynamic change amount). Also, when thenumber of wavelengths used for the light source is set to two (λ1,λ2),different intensity modulation frequencies (f1,f2) are applied to therespective wavelengths and frequency separation is effected by means ofthe lock-in amplifiers, transmitting light intensity signals of theindividual wavelengths can be measured. Accordingly, equation (8) holdsfor the respective wavelengths and a simultaneous equation consisting ofthe following equations (11) and (12) can be introduced:

$\begin{matrix}\begin{matrix}{{\ln\left\lbrack {{{Id}\left( {{\lambda\; 1},t} \right)}/{{Id}^{\prime}\left( {{\lambda\; 1},t} \right)}} \right\rbrack} = {- \left\lbrack {\in {{{{ox}\left( {\lambda\; 1} \right)}\Delta\;{C{ox}}(t)} +}} \right.}} \\{\left. {\in {{deox}\left( {\lambda\; 1} \right)\Delta\;{{C{deox}}(t)}}} \right\rbrack d}\end{matrix} & (11) \\\begin{matrix}{{\ln\left\lbrack {{{Id}\left( {{\lambda\; 2},t} \right)}/{{Id}^{\prime}\left( {{\lambda 2},t} \right)}} \right\rbrack} = {- \left\lbrack {\in {{{{ox}\left( {\lambda\; 2} \right)}\Delta\;{C{ox}}(t)} +}} \right.}} \\{\left. {\in {{deox}\left( {\lambda\; 2} \right)\Delta\;{{C{deox}}(t)}}} \right\rbrack d}\end{matrix} & (12)\end{matrix}$

Since the extinction coefficients ∈ox(λ1), ∈ox(λ2), ∈deox(λ1) and∈deox(λ2) are known, value ΔCox(t)d corresponding to a change amount ofhemoglobin oxide and value ΔCdeox(t) corresponding to a change amount ofreduced hemoglobin can be determined by solving equations (11) and (12)with the computer 213 and time series data representative of adetermined relative change amount can be displayed graphically on thedisplay unit 214. For expansion of the above, the number of wavelengthscan be increased, d can be erased or a relative change amount ofconcentration of a light absorbing substance, other than hemoglobin,which exists in a small amount can be determined.

Alternatively, as shown in FIG. 16, the lock-in amplifiers, logarithmicamplifiers and differential amplifiers may not be used, detectionsignals from the photodetectors 210 a and 210 b may be converted intodigital signals by A/D converters 212, respectively, the digital signalsmay then be FFT processed with the computer 213 to extract only a signalcorresponding to the intensity modulation frequency of the light source,a logarithmic difference between transmitting light intensity levels attwo different detection positions is calculated through a similarprocedure to the above calculation process, and the determined relativechange amount can be displayed graphically as time series data on thedisplay unit 214.

FIGS. 17A and 17B show an example of the light detection probe. FIG. 17Aillustrates a section of the light detection probe and FIG. 17B is adiagram of the light detection probe as viewed from a subject contactsurface.

The light detection probe is comprised of the single light irradiationoptical fiber 204, the two light detection optical fibers 207 a and 207b and the optical fiber fixing member 208 having its surface painted inblack and made of metal or plastics, and the optical fibers areconnected with the optical fiber couplers 203 a, 203 b and 203 c. Inorder to maintain flexibility of the individual optical fibers, eachoptical fiber is constructed of a plurality of optical fibers. As amaterial of the optical fiber, plastics or quartz is used. When thepresent light detection probe is used for a living body, the subjectcontact surface 217 is covered with, for example, resilient sponge.

The size of the detection surface of each light detection optical fibers207 a or 207 b must be changed in accordance with the purpose and thestate of a subject but when measurement of, for example, the cerebralfunction is performed, the sectional shape is made to be a circle havinga diameter of about 1 mm to 20 mm or a square having a side of about 1mm to 20 mm. The two light detection optical fibers 207 a and 207 b aredisposed at positions r (r=5 mm to 50 mm) distant from the lightirradiation optical fiber 204 and here, disposed symmetrically. Aplurality of kinds of light detection probes, in which the distance rdiffers and the sectional shape of each light detection optical fiber207 a or 207 b differs, are prepared and one probe is exchanged withanother in compliance with the purpose of measurement, therebypermitting convenient measurement. Since the light reaching depthsubstantially equals the distance r from the light source, a depthapproximating the cerebral cortex of the cerebrum can be measured fromthe head surface through the skull.

In the light detection probe, various forms of disposition of the lightdetection optical fibers 207 can be conceivable. For example, as shownin FIG. 18, four light detection optical fibers 207 a, 207 b, 207 c and207 d can be disposed at positions r equidistant from the lightirradiation optical fiber 204, and desired two light detection opticalfibers can be selected for measurement. In an alternative, any opticalfiber may not be used but a lens system may be used or a light sourceand photodetectors can be disposed directly in the fixing member 208.

FIG. 19 shows an example where the optical measuring system according tothe present invention is used for measurement of the cerebrum of aliving body. A light detection probe comprised of optical fiber couplers203 a, 203 b and 203 c, a light irradiation optical fiber 204, lightdetection optical fibers 207 a and 207 b, and an optical fiber fixingmember 208 is fixed to a subject 206 by means of a fitting belt 218 madeof rubber. The light irradiation optical fiber 204 is connected to alight source optical fiber 202 through the optical fiber coupler 203 aand the light detection optical fibers 207 a and 207 b are connected tooptical fibers 209 a and 209 b for light detection, respectively,through the optical fiber couplers 203 b and 203 c. Provided on a frontpanel of the optical measuring system 219 are connectors for the lightsource optical fiber 202 and light detection optical fibers 209 a and209 b, an output signal adjusting knob 220, an output signal valueindicating window 221 and a display unit 214. Arranged in the opticalmeasuring system 219 are the differential amplifiers, A/D converters,microprocessor, light source, photodetectors, optical switches and othernecessary electric circuits.

A logarithmic difference signal value between transmitting lightintensity levels detected at two sites is digitally indicated on theoutput signal value indicating window 221 and an offset value of thelogarithmic difference signal value is determined using the outputsignal adjusting knob 220. For example, in the absence of a local changein hemodynamic movement in the cerebrum of the subject, the logarithmicdifference signal between transmitting light intensity levels detectedat the two sites is so adjusted as to be zero. Thereafter, measurementis started and time series data 222 representative of the logarithmicdifference signal is graphically displayed on the display unit 214.Also, the arithmetic operation described previously is carried out tographically display a local hemodynamic amount or time-variable changesin relative change amounts of hemoglobin oxide quantity and reducedhemoglobin quantity.

Embodiment 4

The schematic construction of embodiment 4 of the living body opticalmeasurement system according to the present invention is shown in FIG.20.

Light emitted from a light source 201 is collected using a lens systemso as to impinge on an optical fiber 202 for light source. The lightemitted from the light source is modulated in intensity with a desiredfrequency of about 100 Hz to 10 MHz by means of an oscillator 223 inorder to remove noises due to external disturbance. Since the lightsource optical fiber 202 is connected to an optical fiber 204 for lightirradiation through an optical fiber coupler 203 a, the light from thelight source is transmitted to the light irradiation optical fiber 204and is irradiated on a subject 206 by way of a light irradiationposition 205. The wavelength of the light used depends on spectroscopiccharacteristics of an in vivo substance of interest but when the oxygensaturation amount and the blood amount are measured from concentrationvalues of Hb and HbO2, a single or a plurality of wavelengths can beselected, for use, from light having the wavelength range of from 600 nmto 1400 nm. A semiconductor laser, a titanium/sapphire laser or a lightemitting diode can be used as the light source.

Four light detection optical fibers 207 a, 207 b, 207 c and 207 d fordetecting light transmitting through the subject 206 and going out of itare disposed at four different sites on the subject 206. In the presentembodiment, the two light detection optical fibers 207 b and 207 c aredisposed at two sites which are point symmetrical to a symmetry centerof the light irradiation position 205, the light detection optical fiber207 a is disposed such that the centroid point of the light detectionoptical fiber 207 a is on a half-line having its origin at the centroidpoint of the light irradiation position and passing through the centroidpoint of the light detection optical fiber 207 b, and the lightdetection optical fiber 207 d is disposed such that the centroid pointof the light detection optical fiber 207 d is on a half-line having itsorigin at the centroid point of the light irradiation position andpassing through the centroid point of the light detection optical fiber207 c. The light detection optical fibers 207 a and 207 d can bedisposed anywhere so long as their centroid points are on the half-linesbut in the present embodiment, they are disposed point-symmetrically tothe symmetry center of the light irradiation position 205 and outsidethe light detection optical fibers 207 b and 207 c. Here, the lightirradiation optical fiber 204 and the light detection optical fibers 207a, 207 b, 207 c and 207 d are held in place by means of an optical fiberfixing member 208 made of metal and having its surface painted in black.Since the light detection optical fibers 207 a, 207 b, 207 c and 207 dare connected to optical fibers 209 a, 209 b, 209 c and 209 d forphotodetectors through optical fiber couplers 203 b, 203 c, 203 d and203 e, transmitting light rays detected by the light detection opticalfibers 207 a, 207 b, 207 c and 207 d are transmitted to photodetectors210 a, 210 b, 210 c and 210 d and subjected to photoelectric conversionby the photodetectors 210, so that transmitting light intensity levelssubject to the photoelectric conversion are delivered in the form ofelectric signal intensity levels. Used as the photodetectors 210 arephotoelectric conversion elements such as for example photodiodes orphotomultiplier tubes.

Of electric signals indicative of transmitting light intensity levelsdelivered out of the photodetectors 210 a and 210 b, only frequencycomponents for intensity modulation of the light source are extracted bylock-in amplifiers 224 a and 224 b, respectively. While an output fromthe lock-in amplifier 224 a is subjected to logarithmic conversion by alogarithmic amplifier 225 a and then inputted to the negative pole of adifferential amplifier 211 a, an output from the lock-in amplifier 224 bis subjected to logarithmic conversion by a logarithmic amplifier 225 band subsequently inputted to the positive pole of the differentialamplifier 211 a. Of electric signals indicative of transmitting lightintensity levels delivered out of the photodetectors 210 c and 210 d,only frequency components for intensity modulation of the light sourceare extracted by lock-in amplifiers 224 c and 224 d, respectively. Whilean output from the lock-in amplifier 224 d is subjected to logarithmicconversion by a logarithmic amplifier 225 d and then inputted to thenegative pole of a differential amplifier 211 b, an output from thelock-in amplifier 224 c is subjected to logarithmic conversion by alogarithmic amplifier 225 c and subsequently inputted to the positivepole of the differential amplifier 211 b. Further, an output from thedifferential amplifier 211 a is inputted to the negative pole of adifferential amplifier 211 c and an output from the differentialamplifier 211 b is inputted to the positive pole of the differentialamplifier 211 c. As a result, a difference signal among transmittinglight intensity levels at the four different sites is delivered out ofthe differential amplifier 211 c as an output signal. The output signalfrom the differential amplifier 211 c is sequentially converted into adigital signal by an A/D converter 212, fetched into a computer 213 anddisplayed graphically on a display unit 214 as time series data.

Here, when a region 215 where the hemodynamic movement changes locallyis included in only a view field 216 b of the light detection opticalfiber as shown in FIG. 20, the logarithmic differential signal oftransmitting light intensity delivered out of the differential amplifier211 c reflects only a change in local hemodynamic movement. On thepresupposition that for near infrared rays, hemoglobin serving as a mainconstituent in hemodynamic dominantly acts on extinction, the meaning ofthe logarithmic difference signal delivered out of the differentialamplifier 211 c will be described below.

Where measuring time is t, light source wavelength is λ, irradiationlight intensity is I0(t), concentration values of hemoglobin oxide andreduced hemoglobin are Cox(t) and Cdeox(t), respectively, changes inconcentration values of hemoglobin oxide and reduced hemoglobin whichoccur at the local region 215 are ΔCox(t) and ΔCdeox(t), respectively,extinction coefficients for light source wavelength λ of hemoglobinoxide and reduced hemoglobin are ∈ox(λ) and ∈deox(λ), respectively,attenuation contained in transmitting light intensity levels detected bythe photodetectors 210 b and 210 c and due to scattering and absorptioncaused by other constituents than hemoglobin is Ds1, attenuationcontained in transmitting light intensity levels detected by thephotodetectors 210 a and 210 d and due to scattering and absorptioncaused by other constituents than hemoglobin is Ds2, weight coefficientcontained in the transmitting light intensity levels detected by thephotodetectors 210 b and 210 c and caused by scattering is d1, andweight coefficient contained in the transmitting light intensity levelsdetected by the photodetectors 210 a and 210 d and caused by scatteringis d2, transmitting light intensity signal Id1(t) detected by thephotodetector 210 c, transmitting light intensity signal Id2(t) detectedby the photodetector 210 d, transmitting light intensity signal Id1′(t)detected by the photodetector 210 b and transmitting light intensitysignal Id2′(t) detected by the photodetector 210 a are given by thefollowing equations (13) to (16):

$\begin{matrix}\begin{matrix}{{{Id}\; 1(t)} = {{Ds}\;{1 \cdot {\exp\left\lbrack {- \left\lbrack {\in {{{{ox}(\lambda)}\left( {{{C{ox}}(t)} + {\Delta\;{{C{ox}}(t)}}} \right)} +}} \right.} \right.}}}} \\{\left. {\left. {\in {{deox}(\lambda)\left( {{{C{deox}}(t)} + {\Delta\;{{C{deox}}(t)}}} \right)}} \right\rbrack d\; 1} \right\rbrack I\; 0(t)}\end{matrix} & (13) \\\begin{matrix}{{{Id}\; 2(t)} = {{Ds}\;{2 \cdot {\exp\left\lbrack {- \left\lbrack {\in {{{{ox}(\lambda)}\left( {{{C{ox}}(t)} + {\Delta\;{{C{ox}}(t)}}} \right)} +}} \right.} \right.}}}} \\{\left. {\left. {\in {{deox}(\lambda)\left( {{{C{deox}}(t)} + {\Delta\;{{C{deox}}(t)}}} \right)}} \right\rbrack d\; 2} \right\rbrack I\; 0(t)}\end{matrix} & (14) \\\begin{matrix}{{{Id}\; 1^{\prime}(t)} = {{Ds}\;{1 \cdot {\exp\left\lbrack {- \left\lbrack {\in {{{{ox}(\lambda)}{C{ox}}(t)} +}} \right.} \right.}}}} \\{\left. {\left. {\in {{deox}(\lambda){{C{deox}}(t)}}} \right\rbrack d\; 1} \right\rbrack I\; 0(t)}\end{matrix} & (15) \\\begin{matrix}{{{Id}\; 2^{\prime}(t)} = {{Ds}\;{2 \cdot {\exp\left\lbrack {- \left\lbrack {\in {{{{ox}(\lambda)}{C{ox}}(t)} +}} \right.} \right.}}}} \\{\left. {\left. {\in {{deox}(\lambda){{C{deox}}(t)}}} \right\rbrack d\; 2} \right\rbrack I\; 0(t)}\end{matrix} & (16)\end{matrix}$

Next, equations (13) and (14) are expressed in terms of naturallogarithm and then equation (14) is subtracted from equation (13) toobtain the following equation (17):

$\begin{matrix}\begin{matrix}{{\ln\left\lbrack {{Id}\; 1{(t)/{Id}}\; 2(t)} \right\rbrack} = {{\ln\left\lbrack {{Ds}\;{1/{Ds}}\; 2} \right\rbrack} - \left\lbrack {\in {{{ox}(\lambda)}\left( {{{C{ox}}(t)} +} \right.}} \right.}} \\{{\left. {\Delta\;{C{ox}}(t)} \right) +} \in {{deox}(t)\left( {{{C{deox}}(t)} +} \right.}} \\{\left. \left. {\Delta\;{C{deox}}(t)} \right) \right\rbrack\left( {{d\; 1} - {d\; 2}} \right)}\end{matrix} & (17)\end{matrix}$

Equations (15) and (16) are expressed in terms of natural logarithm andthen equation (16) is subtracted from equation (15) to obtain thefollowing equation (18):

$\begin{matrix}\begin{matrix}{{\ln\left\lbrack {{Id}\; 1^{\prime}{(t)/{Id}}\; 2^{\prime}(t)} \right\rbrack} = {{{\ln\left\lbrack {{Ds}\;{1/{Ds}}\; 2} \right\rbrack} -} \in {{{ox}(\lambda)}\left( {{{C{ox}}(t)} +} \right.}}} \\{{\left. {\Delta\;{C{ox}}(t)} \right) +} \in {{{deox}(\lambda)}\left( {{{C{deox}}(t)} +} \right.}} \\{\left. \left. {\Delta\;{C{deox}}(t)} \right) \right\rbrack\left( {{d\; 1} - {d\; 2}} \right)}\end{matrix} & (18)\end{matrix}$

The left side of equation (17) represents the output of the differentialamplifier 211 b and the left side of equation (18) represents the outputof the differential amplifier 211 a. Here, by subtracting equation (18)from equation (17), the following equation (19) is obtained:

$\begin{matrix}\begin{matrix}{{\ln\left\lbrack {\left( {{Id}\; 1{(t)/{Id}}\; 2(t)} \right)\left( {{Id}\; 2^{\prime}{(t)/{Id}}\; 1^{\prime}(t)} \right.} \right\rbrack} = {- \left\lbrack {\in {{{{ox}(\lambda)}\Delta\;{C{ox}}(t)} +}} \right.}} \\{\left. {\in {{deox}(\lambda)}} \right\rbrack\left( {{d\; 1} - {d\; 2}} \right)}\end{matrix} & (19)\end{matrix}$

The left side of equation (19) represents the output of the differentialamplifier 211 c, that is, the measured logarithmic difference signal.

Here, when 805 nm±10 nm is particularly used as the light sourcewavelength for measurement, the aforementioned relation of equation (9)stands and by using constant K, equation (19) can be reduced to thefollowing equation (20):

$\begin{matrix}{{\ln\left\lbrack {\left( {{Id}\; 1{(t)/{Id}}\; 2(t)} \right)\left( {{Id}\; 2^{\prime}{(t)/{Id}}\; 1^{\prime}(t)} \right)} \right\rbrack} = {{- \left\lbrack {{\Delta\;{{C{ox}}(t)}} + {\Delta\;{{C{deox}}(t)}}} \right\rbrack} \cdot K}} & (20)\end{matrix}$

Accordingly, the logarithmic difference signal measured using the lightsource wavelength 805 nm±10 nm represents a value corresponding to arelative hemodynamic change amount [ΔCox(t)+ΔCdeox(t)].

Also, when the number of wavelengths used for the light source is two(λ1,λ2), different intensity modulation frequencies (f1,f2) are appliedto the respective wavelengths and frequency separation is effected bymeans of the lock-in amplifiers, transmitting light intensity signals ofthe individual wavelengths can be measured. Accordingly, equation (19)holds for the respective wavelengths and a simultaneous equationconsisting of the following equations (21) and (22) can be introduced:

$\begin{matrix}{{\ln\left\lbrack {\left( {{Id}\; 1{\left( {{\lambda\; 1},t} \right)/{Id}}\; 2\left( {{\lambda\; 1},t} \right)} \right)\left( {{Id}\; 2^{\prime}{\left( {{\lambda\; 1},t} \right)/{Id}}\; 1^{\prime}\left( {{\lambda 1},t} \right)} \right)} \right\rbrack} = {{- \left\lbrack {\in {{{{ox}\left( {\lambda\; 1} \right)}\Delta\;{{C{ox}}(t)}} +} \in {{{deox}({\lambda 1})}\Delta\;{{C{deox}}(t)}}} \right\rbrack}\left( {{d\; 1} - {d\; 2}} \right)}} & (21) \\{{\ln\left\lbrack {\left( {{Id}\; 1{\left( {{\lambda\; 2},t} \right)/{Id}}\; 2\left( {{\lambda\; 2},t} \right)} \right)\left( {{Id}\; 2^{\prime}{\left( {{\lambda\; 2},t} \right)/{Id}}\; 1^{\prime}\left( {{\lambda 2},t} \right)} \right)} \right\rbrack} = {{- \left\lbrack {\in {{{{ox}\left( {\lambda\; 2} \right)}\Delta\;{{C{ox}}(t)}} +} \in {{{deox}({\lambda 2})}\Delta\;{{C{deox}}(t)}}} \right\rbrack}\left( {{d\; 1} - {d\; 2}} \right)}} & (22)\end{matrix}$

Since the extinction coefficients ∈ox(λ1), ∈ox(λ2), ∈deox(λ1) and∈deox(λ2) are known, value ΔCox(t)(d1-d2) corresponding to a changeamount of hemoglobin oxide and value ΔCdeox(t)(d1-d2) corresponding to achange amount of reduced hemoglobin can be determined by solvingequations (21) and (22) with the computer 213 and time series datarepresentative of a determined relative change amount can be displayedgraphically on the display unit 214. For expansion of the above, thenumber of wavelengths can be increased, (d1-d2) can be erased or arelative change amount of concentration of a light absorbing substance,other than hemoglobin, which exists in a small amount can be determined.

Alternatively, as shown in FIG. 21, the lock-in amplifiers, logarithmicamplifiers and differential amplifiers may not be used, detectionsignals from the photodetectors 210 a, 210 b, 210 c and 210 d may beconverted into digital signals by the A/D converters 212, respectively,the digital signals may then be FFT processed with the computer 213 toextract only a signal corresponding to the intensity modulationfrequency of the light source, a logarithmic difference amongtransmitting light intensity levels at four different detectionpositions may be calculated through a similar procedure to the abovecalculation process, and then the determined relative change amount canbe displayed graphically as time series data on the display unit 214.

Embodiment 5

The schematic construction of embodiment 5 of the living body opticalmeasurement system according to the present invention is shown in FIG.22.

Light rays emitted from light sources 201 a and 201 b are collectedusing lens systems so as to impinge on an optical fiber 202 a for lightsource and an optical fiber 202 b for light source, respectively. Thelight rays emitted from the respective light sources are modulated inintensity with desired different frequencies f of about 100 Hz to 10 MHzby means of oscillators 223 a and 223 b in order to remove noises due toexternal disturbance. Here, the intensity modulation frequency for thelight source 201 a is set to f1 and the intensity modulation frequencyfor the light source 201 b is set to f2. Since the light source opticalfiber 202 a is connected to an optical fiber 204 a for light irradiationthrough an optical fiber coupler 203 a and the light source opticalfiber 202 b is connected to an optical fiber 204 b for light irradiationthrough an optical fiber coupler 203 c, the light rays from therespective light sources are transmitted to the light irradiationoptical fibers 204 a and 204 b and irradiated on a subject 206 by way oflight irradiation positions 205 a and 205 b. In order to obtainreference light rays, the light is split at a halfway point of each ofthe light irradiation optical fibers 204 a and 204 b by means of asplitter 226 a or 226 b and the intensity of each light source isconverted into an electric signal by means of a photodetector 210 a or210 c. A reference light intensity signal for the light source 201 a,delivered out of the photodetector 210 a, is inputted to a lock-inamplifier 224 a and separated on the basis of a reference frequency fromthe oscillator 223 a. An output of the lock-in amplifier 224 a isinputted to a logarithmic amplifier 225 a so as to undergo logarithmicconversion and then inputted to the negative pole of a differentialamplifier 211 a. A reference light intensity signal for the light source201 b, delivered out of the photodetector 210 c, is inputted to alock-in amplifier 224 d and separated on the basis of a referencefrequency from the oscillator 223 b. An output of the lock-in amplifier224 d is inputted to a logarithmic amplifier 225 d so as to undergologarithmic conversion and then inputted to the negative pole of adifferential amplifier 211 b. The wavelength of the light used dependson spectroscopic characteristics of an in vivo substance of interest butwhen the oxygen saturation amount and the hemodynamic amount aremeasured from concentration values of Hb and HbO2, a single or aplurality of wavelengths can be selected, for use, from light having thewavelength range of from 600 nm to 1400 nm. A semiconductor laser, atitanium/sapphire laser or a light emitting diode can be used as thelight source.

For detection of light transmitting through a subject 206 and going outof it, one optical fiber 207 for light detection is disposed at aposition on the subject 206 which is equidistant from light irradiationpositions 205 a and 205 b. Here, the light irradiation optical fibers204 a and 204 b and the light detection optical fiber 207 are held inplace by means of an optical fiber fixing member 208 having its surfacepainted in black. Since the light detection optical fiber 207 isconnected to an optical fiber 209 for light detection through an opticalfiber coupler 203 b, transmitting light detected by the light detectionoptical fiber 207 is transmitted to a photodetector 210 b and subjectedto photoelectric conversion by the photodetector 210 b, so that thetransmitting light intensity is delivered in the form of electricalsignal intensity. Used as the photodetector 210 b is a photoelectricconversion element such as for example a photodiode or a photomultipliertube.

Since the electric signal representative of the transmitting lightintensity level delivered out of the photodetector 210 b contains thetransmitting light intensity signal for the light source 201 a and thetransmitting light intensity signal for the light source 201 b, only anintensity modulation frequency component for the light source 201 a isextracted by a lock-in amplifier 224 b and only an intensity modulationfrequency component signal for the light source 201 b is extracted by alock-in amplifier 224 c. An output from the lock-in amplifier 224 b issubjected to logarithmic conversion by a logarithmic amplifier 225 b andthen inputted to the positive pole of the differential amplifier 211 a.An output from the lock-in amplifier 224 c is subjected to logarithmicconversion by a logarithmic amplifier 225 c and subsequently inputted tothe positive pole of the differential amplifier 211 b. As a result, alogarithmic difference signal between the intensity of the light source201 a and the transmitting light intensity for the light source 201 a isdelivered out of the differential amplifier 211 a as an output signal,and a logarithmic difference signal between the intensity of the lightsource 201 b and the transmitting light intensity for the light source201 b is delivered out of the differential amplifier 211 b as an outputsignal. Further, an output from the differential amplifier 211 a isinputted to the negative pole of a differential amplifier 211 c and anoutput from the differential amplifier 211 b is inputted to the positivepole of the differential amplifier 211 c, so that a logarithmicdifferential signal between transmitting light intensity levels which isremoved of fluctuation in the light source intensity can be deliveredout of the differential amplifier 211 c. The output signal from thedifferential amplifier 211 c is sequentially converted into a digitalsignal by an A/D converter 212, fetched into a computer 213 anddisplayed on a display unit 214 as time series data.

Here, when a region 215 where the hemodynamic movement changes locallyis included in only a view field 216 b of the light detection opticalfiber as shown in FIG. 22, the measured logarithmic differential signalreflects only a change in local hemodynamic movement. On thepresupposition that for near infrared rays, hemoglobin serving as a mainconstituent in hemodynamic dominantly acts on extinction, the meaning ofthe measured logarithmic difference signal will be described below.

Where measuring time is t, light source wavelength is λ, irradiationlight intensity from the irradiation position 205 b is I0(t),irradiation light intensity from the irradiation position 205 a isI0′(t), reference light intensity from the splitter 226 b is Ir(t),reference light intensity from the splitter 226 b is Ir′(t), ratio ofsplitting to reference light of the splitter is α indicating thatI0(t):Ir(t)=I0′(t):Ir′(t)=1:α,concentration values of hemoglobin oxide and reduced hemoglobin areCox(t) and Cdeox(t), respectively, changes in concentration values ofhemoglobin oxide and reduced hemoglobin which occur at the local region215 are ΔCox(t) and ΔCdeox, respectively, extinction coefficients forlight source wavelength λ of hemoglobin oxide and reduced hemoglobin are∈ox(λ) and ∈deox(λ), respectively, attenuation due to scattering andabsorption caused by other constituents than hemoglobin is Ds, andweight coefficient caused by scattering is d, transmitting lightintensity signal Id(t) for the light source 201 b detected by thephotodetector 210 b, that is, the output from the lock-in amplifier 224c is given by the following equation (23) and transmitting lightintensity signal Id′(t) for the light source 201 a, that is, the outputfrom the lock-in amplifier 224 b is given by the following equation(24):

$\begin{matrix}\begin{matrix}{{{Id}(t)} = {{Ds} \cdot \mspace{11mu}{\exp\left\lbrack {- \left\lbrack {\varepsilon\;{{ox}(\lambda)}\left( {{{Cox}(t)} + {\Delta\;{{Cox}(t)}} +} \right.} \right.} \right.}}} \\{\left. {\left. {\varepsilon\;{{deox}(\lambda)}\left( {{{Cdeox}(t)} + {\Delta\;{{Cdeox}(t)}}} \right)} \right\rbrack d} \right\rbrack{{I0}(t)}}\end{matrix} & (23) \\\begin{matrix}{{{Id}^{\prime}(t)} = {{Ds} \cdot \mspace{11mu}{\exp\left\lbrack {- \left\lbrack {\varepsilon\;{{ox}(\lambda)}\left( {{{Cox}(t)} +} \right.} \right.} \right.}}} \\{\left. {\left. {\varepsilon\;{{deox}(\lambda)}{{Cdeox}(t)}} \right\rbrack d} \right\rbrack{{I0}^{\prime}(t)}}\end{matrix} & (24)\end{matrix}$

Next, equations (23) and (24) are expressed in terms of naturallogarithm and then equation (23) is reduced to the following equation(25) and equation (24) is reduced to the following equation (26):

$\begin{matrix}{{\ln\left\lbrack {{{Id}(t)}/{{I0}(t)}} \right\rbrack} = {{\ln\lbrack{Ds}\rbrack} - \left\lbrack {\varepsilon\;{{ox}(\lambda)}\left( {{{Cox}(t)} + {\Delta\;{{Cox}(t)}} +} \right.} \right.}} & (25) \\{\left. \mspace{185mu}{\varepsilon\;{{deox}(\lambda)}\left( {{C\;{{deox}(t)}} + {\Delta\;{{Cdeox}(t)}}} \right)} \right\rbrack d} & \; \\{{\ln\left\lbrack {{{Id}^{\prime}(t)}/{{I0}^{\prime}(t)}} \right\rbrack} = {{\ln\lbrack{Ds}\rbrack} - \left\lbrack {\varepsilon\;{{ox}(\lambda)}\left( {{{Cox}(t)} +} \right.} \right.}} & (26) \\{\left. \mspace{200mu}{\varepsilon\;{{deox}(\lambda)}C\;{{deox}(t)}} \right\rbrack d} & \;\end{matrix}$

Further, equation (26) is subtracted from equation (25) to obtain thefollowing equation (27):

$\begin{matrix}\begin{matrix}{\ln\left\lbrack {{\left( {{{Id}(t)}/{{Id}^{\prime}(t)}} \right)\left( {{{I0}^{\prime}(t)}/{{I0}(t)}} \right\rbrack} =} \right.} \\{{- \left\lbrack {{\varepsilon\;{{ox}(\lambda)}\Delta\;{{Cox}(t)}} + {\varepsilon\;{{deox}(\lambda)}\Delta\; C\;{{deox}(t)}}} \right\rbrack}d} \\{{Here},}\end{matrix} & (27) \\{{{Ir}(t)} = {\alpha\;{{I0}(t)}}} & (28) \\{{{{Ir}^{\prime}(t)} = {\alpha\;{{I0}^{\prime}(t)}}}\;} & (29)\end{matrix}$stand and therefore, the output from the differential amplifier 211 a isln[Id′(t)/αI0′(t)]and the output from the differential amplifier 211 c isln[(Id(t)/Id′(t))(I0′(t)/I0′(t)]  (30)Since equation (30) equals the left side of equation (27), thelogarithmic difference signal delivered out of the differentialamplifier 211 c is equivalent to equation (27).

Here, when 805 nm±10 nm is particularly used as the light sourcewavelength for measurement, the aforementioned relation of equation (9)stands and by using constant K, equation (27) can be reduced to thefollowing equation (31):

$\begin{matrix}{{\ln\left\lbrack {\left( {{{Id}(t)}/{{Id}^{\prime}(t)}} \right)\left( {{{I0}^{\prime}(t)}/{{I0}(t)}} \right)} \right\rbrack} =} & (31) \\{{- \left\lbrack {{\Delta\;{{Cox}(t)}} + {\Delta\;{{Cdeox}(t)}}} \right\rbrack}K} & \;\end{matrix}$

Accordingly, the logarithmic difference signal measured using the lightsource wavelength 805 nm±10 nm represents a value corresponding to arelative hemodynamic change amount [ΔCox(t)+ΔCdeox(t)]−K. Also, when thenumber of wavelengths used for the light source is two (λ1,λ2),intensity modulation frequencies (f1, f2, f3, f4) which differ with therespective wavelengths and the respective irradiation positions areapplied and frequency separation is effected by means of the lock-inamplifiers, transmitting light intensity signals for the individualwavelengths and the respective irradiation positions can be measured.Accordingly, equation (27) holds for the respective wavelengths and asimultaneous equation consisting of the following equations (32) and(33) can be introduced:

$\begin{matrix}{{\ln\left\lbrack {\left( {{{Id}\left( {{\lambda\; 1}\;,t} \right)}/{{Id}^{\prime}\left( {{\lambda 1},t} \right)}} \right)\left( {{{I0}^{\prime}\left( {{\lambda 1},t} \right)}/{{I0}\left( {{\lambda 1},t} \right)}} \right)} \right\rbrack} =} & (32) \\{{- \left\lbrack {{\varepsilon\;{{ox}({\lambda 1})}\Delta\;{{Cox}(t)}} + {\varepsilon\;{{deox}({\lambda 1})}\Delta\; C\;{{deox}(t)}}} \right\rbrack}d} & \; \\{{\ln\left\lbrack {\left( {{{Id}\left( {{\lambda 2},t} \right)}/{{Id}^{\prime}\left( {{\lambda 2},t} \right)}} \right)\left( {{{I0}^{\prime}\left( {{\lambda 2},t} \right)}/{{I0}\left( {{\lambda 2},t} \right)}} \right)} \right\rbrack} =} & (33) \\{{- \left\lbrack {{\varepsilon\;{{ox}({\lambda 2})}\Delta\;{{Cox}(t)}} + {\varepsilon\;{{deox}({\lambda 2})}\Delta\; C\;{{deox}(t)}}} \right\rbrack}d} & \;\end{matrix}$

Since the extinction coefficients ∈ox(λ1), ∈ox(λ2), ∈deox(λ1) and∈deox(λ2) are known, value ΔCox(t)d corresponding to a change amount ofhemoglobin oxide and ΔCdeox(t) corresponding to a change amount ofreduced hemoglobin can be determined by solving equations (32) and (33)with the computer 213 and time series data representative of adetermined relative change amount can be displayed graphically on thedisplay unit 214. For expansion of the above, the number of wavelengthscan be increased, d can be erased or a relative change amount ofconcentration of a light absorbing substance, other than hemoglobin,which exists in a small amount can be determined.

Alternatively, as shown in FIG. 23, the lock-in amplifiers, logarithmicamplifiers and differential amplifiers may not be used, detectionsignals from the photodetectors 210 a, 210 b and 210 c may be convertedinto digital signals by the A/D converters 212, respectively, thedigital signals may then be FFT processed with the computer 213 toextract only signals corresponding to intensity modulation frequenciesof the respective light sources, a relative change amount calculated anddetermined through a similar procedure to the above calculation processcan be displayed graphically as time series data on the display unit214.

In the present invention, since the low cost light irradiation means andphotodetectors are used to realize the simplified arithmetic processing,the high-speed processing can be ensured with an economical system andthe living body function in correspondence to a plane image illustrativeof the shape of an object to be measured can be imaged, thus ensuringthat means effective especially for measurement of the local function ofliving body can be provided.

According to the prior arts, when the hemodynamic movement of a subjectis measured by alternately repeating unloading and loading, thereference value varies and correct measurement cannot be carried outunless the measurement is delayed until signals to be measured arestabilized by keeping the subject quiet. According to the measuringmethod of the present invention, measurement can be conducted withoutwaiting for the stabilization of signals. Further, measured signals canbe removed of fluctuation to promote accuracy of signals.

When the first and second detection positions are set at locations whichare substantially equidistant from the light irradiation position,transmitting light intensity signals at the respective detectionpositions equally change with an overall change in hemodynamic movementin a living body. Accordingly, by taking a logarithmic differencebetween a transmitting light intensity signal at the first detectionposition and a transmitting light intensity signal at the seconddetection position, a signal change attributable to the overallhemodynamic movement change can be removed. Further, when a changeattributable to local hemodynamic movement is included in only one oftransmitting light intensity signals at the first and second detectionpositions, the transmitting light intensity logarithmic differencesignal reflects only the local change in hemodynamic movement.

The light ray comes into the living body through the light irradiationposition and passes through complicated paths while interacting withvarious tissues of the living body and undergoing scattering andattenuation before it goes out of the living body through the lightdetection position. In the present invention, since the logarithmicdifference between light intensity levels going out of the living bodythrough positions which are substantially equidistant from the lightirradiation position, the influence of scattering and attenuation causedby the tissues of the living body can be cancelled out and a slightsignal reflecting the local change in hemodynamic movement can bedetected with high accuracy.

Concretely, when an operation for cutting off a portion of the cerebrumis conducted in determination of the focus of epilepsy and therapy ofserious epilepsy, an image of the portion to be cut off can be used toconfirm that the cutting-off portion is a portion which does not impairthe important in vivo function of the subject.

1. A living body optical measurement system comprising: an irradiationunit adapted to irradiate light on a living body while alternatelysetting loading time during which load is applied to the living body andunloading time during which load is not applied to the living body, ameasurement unit adapted to measure the living body transmitting lightintensity by irradiating the light on the living body to obtain ameasured signal, an arithmetic unit adapted to calculate a signal whichcorresponds to the fluctuation due to hemodynamic movement in the livingbody during a relaxation time, wherein the relaxation time is the timeduring which the signal has time to recover its intact form followingthe loading time and in which influence by application of the loadremains during the unloading time, and wherein the calculation is doneby eliminating the measured signal from the relaxation time and fittinga predetermined function, through use of a method of least squares, tothe remaining unloading-time portions of the measured signal, and adisplay unit adapted to display a result calculated by said arithmeticunit.
 2. A living body optical measurement system according to claim 1,wherein said arithmetic unit is adapted to calculate a differencebetween the measured signal and the obtained signal due to the change inthe hemodynamic movement, to display the difference by said displayunit.
 3. A living body optical measurement system according to claim 1,wherein said display unit is adapted to display the measured signal andthe obtained signal due to the change in the hemodynamic movement.
 4. Aliving body optical measurement system according to claim 1, whereinsaid display unit is adapted to display a mark indicative of a startingpoint of applying said load and a mark indicative of an end point ofapplying said load in the form of straight lines.
 5. A living bodyoptical measurement system according to claim 1, wherein said arithmeticunit is adapted to perform calculation for determining time-variablechanges of relative change amounts of concentration of hemoglobin oxideand reduced hemoglobin, due to said load on the basis of the measuredsignal and the obtained signal due to the change in the hemodynamicmovement, and wherein said display unit is adapted to display thetime-variable changes of relative change amounts of concentration ofhemoglobin oxide and reduced hemoglobin, determined by said arithmeticunit.
 6. A living body optical measurement system according to claim 5,wherein said arithmetic unit is adapted to perform the calculation fordetermining a time integral value in each of the loading time or a meanvalue in each of the loading time, of each of time-variable changes ofthe relative change amounts of the hemoglobin oxide and the reducedhemoglobin, and wherein said display unit is adapted to display the timeintegral value and the mean value.
 7. A living body optical measurementsystem comprising: an irradiation unit adapted to irradiate light on aliving body while alternately setting loading time during which load isapplied to the living body and unloading time during which load is notapplied to the living body, a measurement unit adapted to measure theliving body transmitting light intensity by irradiating the light on theliving body to obtain a measured signal, an arithmetic unit adapted tocalculate a signal which corresponds to the fluctuation due tohemodynamic movement in the living body during a relaxation time,wherein the relaxation time is the time during which the signal has timeto recover its intact form following the loading time and in whichinfluence by application of the load remains during the unloading time,and wherein the calculation is done by eliminating the measured signalfrom the relaxation time and fitting a predetermined function, throughuse of a method of least squares, to the remaining unloading-timeportions of the measured signal, and a display unit adapted to display aresult calculated by said arithmetic unit, wherein said arithmetic unitis adapted to perform said fitting to the measured signal during twounloading times before and after each loading time from which themeasured signal during the relaxation time is eliminated.
 8. A livingbody optical measurement system comprising: an irradiation unit adaptedto irradiate light on a living body while alternately setting loadingtime during which load is applied to the living body and unloading timeduring which load is not applied to the living body, a measurement unitadapted to measure the living body transmitting light intensity byirradiating the light on the living body to obtain a measured signal, anarithmetic unit adapted to calculate a signal which corresponds to thefluctuation due to hemodynamic movement in the living body during arelaxation time, wherein the relaxation time is the time during whichthe signal has time to recover its intact form following the loadingtime and in which influence by application of the load remains duringthe unloading time, and wherein the calculation is done by eliminatingthe measured signal from the relaxation time and fitting a predeterminedfunction, through use of a method of least squares, to the remainingunloading-time portions of the measured signal, and a display unitadapted to display a result calculated by said arithmetic unit, whereinsaid arithmetic unit is adapted to perform said fitting to the measuredsignal during a plurality of unloading times from which the measuredsignal during the relaxation time is eliminated.
 9. A living bodyoptical measurement system comprising: a plurality of light sourcesadapted to simultaneously irradiate a plurality of light rays havingwavelengths different from each other on a head of a living body, adetector unit adapted to detect intensities of the light rays after thelight rays irradiated on the head of the living body are transmittedthrough the living body, and adapted to separate the living bodytransmitting light rays with respect to each wavelength to measure theintensity of the separated light to obtain a measured signal withrespect to each wavelength, an arithmetic unit adapted to performcalculation for obtaining a signal due to a change in hemodynamicmovement in the head with respect to each wavelength on a basis of adetected result of said detector unit, a display unit adapted to displaycalculated results of said arithmetic unit, and an input unit, whereinsaid arithmetic unit is adapted to calculate a signal which correspondsto the fluctuation due to hemodynamic movement in the head during arelaxation time, wherein the relaxation time is the time during whichthe measured signal has time to recover its intact form following theloading time and in which influence by application of the load remainsduring the unloading time, and wherein the calculation is done byeliminating the measured signal from the relaxation time and fitting apredetermined function, through use of a method of least squares, to theremaining unloading-time portions of the measured signal, and whereinsaid display unit displays the signal due to the change in hemodynamicmovement in the head calculated by said arithmetic unit and saidmeasured signal.
 10. A living body optical measurement systemcomprising: a plurality of light sources adapted to irradiate aplurality of light rays having wavelengths different from each other ona living body, a detector unit adapted to detect intensities of thelight rays after the light rays from said light sources irradiated onthe living body, are transmitted through the living body, to obtain aplurality of measured signals, a computer adapted to calculate a signalwhich corresponds to the fluctuation due to hemodynamic movement in theliving body during a relaxation time, wherein the relaxation time is thetime during which the plurality of measured signals have time to recoverits intact form following the loading time and in which influence byapplication of the load remains during the unloading time, and whereinthe calculation is done by eliminating the plurality of measured signalsfrom the relaxation time and fitting a predetermined function, throughuse of a method of least squares, to the remaining unloading-timeportions of the plurality of measured signals, and a display unitadapted to display results calculated by said computer.
 11. A livingbody optical measurement system according to claim 10, wherein saidcomputer is adapted to calculate a difference between the measuredsignal of said detector unit and the fluctuation signals of the livingbody calculated by said computer, and wherein said display unit isadapted to display the difference.
 12. A living body optical measurementsystem according to claim 10, wherein said display unit is adapted todisplay the measured signal of said detector unit and the fluctuationsignals of the living body, calculated by said computer.
 13. A livingbody optical measurement system according to claim 10, wherein saiddisplay unit is adapted to display a mark indicative of a starting pointof applying said load, and a mark indicative of an end point of applyingsaid load, in the form of straight lines.
 14. A living body opticalmeasurement system according to claim 10, wherein said computer isadapted to perform calculation for determining time-variable changes ofrelative change amounts of concentration of hemoglobin oxide and reducedhemoglobin, due to said load on a basis of the measured signal and theobtained said fluctuation signals of the living body, and wherein saiddisplay unit is adapted to display the time-variable changes of relativechange amounts of concentration of hemoglobin oxide and reducedhemoglobin, determined by said computer.
 15. A living body opticalmeasurement system according to claim 14, wherein said computer isadapted to perform the calculation for determining a time integral valuein each of the loading time, or a mean value in each of the loadingtime, of each of time-variable changes of the relative change amounts ofthe hemoglobin oxide and the reduced hemoglobin, and wherein saiddisplay unit is adapted to display the time integral value and the meanvalue.
 16. A living body optical measurement system comprising: aplurality of light sources adapted to irradiate a plurality of lightrays having wavelengths different from each other on a living body, adetector unit adapted to detect intensities of the light rays after thelight rays from said light sources irradiated on the living body, aretransmitted through the living body, to obtain a plurality of measuredsignals, a computer adapted to calculate a signal which corresponds tothe fluctuation due to hemodynamic movement in the living body during arelaxation time, wherein the relaxation time is the time during whichthe plurality of measured signals have time to recover its intact formfollowing the loading time and in which influence by application of theload remains during the unloading time, and wherein the calculation isdone by eliminating the plurality of measured signals from therelaxation time and fitting a predetermined function, through use of amethod of least squares, to the remaining unloading-time portions of theplurality of measured signals, and a display unit adapted to displayresults calculated by said computer, wherein said computer is adapted toperform fitting through use of a method of least squares to the measuredsignal in two unloading times before and after each of the loading timeand not including the relaxation time.
 17. A living body opticalmeasurement system comprising: a plurality of light sources adapted toirradiate a plurality of light rays having wavelengths different fromeach other on a living body, a detector unit adapted to detectintensities of the light rays after the light rays from said lightsources irradiated on the living body, are transmitted through theliving body, to obtain a plurality of measured signals, a computeradapted to calculate a signal which corresponds to the fluctuation dueto hemodynamic movement in the living body during a relaxation time,wherein the relaxation time is the time during which the plurality ofmeasured signals have time to recover its intact form following theloading time and in which influence by application of the load remainsduring the unloading time, and wherein the calculation is done byeliminating the plurality of measured signals from the relaxation timeand fitting a predetermined function, through use of a method of leastsquares, to the remaining unloading-time portions of the plurality ofmeasured signals, and a display unit adapted to display resultscalculated by said computer, wherein said computer is adapted to performfitting through use of a method of least squares to the measured signalin a plurality of unloading times, from which the measured signal in therelaxation time is removed.